Pharmacologically active quinazolinone compound, its use in pharmacological preparations and process for its preparation

ABSTRACT

2-Methyl-3-(N-( 3-(4-phenylpiperazinyl-(1))-2-hydroxypropyl(1))-anilino)quinazolinone-(4) and its non-toxic acid addition salts which have a strong cataleptic activity.

United States Patent Boltze et al.

[4 1 June 13, 1972 [54] PHARMACOLOGICALLY ACTIVE QUINAZOLINONE COMPOUND, ITS USE IN PHARMACOLOGICAL PREPARATIONS AND PROCESS FOR ITS PREPARATION [72] Inventors: Karl-Heniz Boltze, Bensberg-Kippekausen; Dietrich Lorenz, Kleinhurden, Post B. Bensberg, both of Gem'iany [73] Assignee: Troponwerke Dinklage & Co., Berliner Strasse, Cologne-Mulheim, Germany [22] Filed: July 15, 1970 21 Appl. No.: 55,247

[30] Foreign Application Priority Data July 18, 1969 Germany ..P 19 36 588.9

Wagner et al. Synthetic Organic Chemistry Wiley and Sons, Inc.- New York- 195 3- pp. 666- 67, 672

Primary ExaminerAlex Mazel Assistant Examiner-R. V. Rush AnorneyBurgess, Dinklage & Sprung [57] ABSTRACT 2-Methyl-3- {N-[3-(4-phenylpiperazinyl-( 1 ))-2-hydroxypropyl-( l )]-anilino} quinaz0linone-(4) and its non-toxic acid addition salts which have a strong cataleptic activity.

2 Claims, No Drawings PHARMACOLOGICALLY ACTIVE QUINAZOLINONE COMPOUND, ITS USE IN PHARMACOLOGICAL PREPARATIONS AND PROCESS FOR ITS PREPARATION This invention relates to a pharmacologically active quinazolinone compound, its use in pharmacological preparations and process for its preparation.

Quinazolinone derivatives are already known for their use in human medicine as sedatives, anticonvulsants and hypnotics, the substituents in such derivatives being present in the 2- and/or 3-position.

It has now surprisingly been found that by further variation of the substituents, a compound which has a neuroleptic'activity is obtained.

2-Methyl-3-{N-[3-( 4-phenylpiperazinyl-( 1 )-2-hydroxypropyl-( l )]-ani1ino}-quinazolinone-( 4) of formula I shows a powerful cataleptic activity both in rats and in mice when administered per os in doses of 2 mg/kg or more. In addition, it has antioedematous and hypotensive activities. As can be shown by animal experiments, the mechanism of its action is based on a reduction of the catecholamine level in the central nervous system, which is greater than the reduction brought about by reserpine.

The toxicity of the substance is low compared with the effective dose, the LD values being 60 to 70 mg/kg for intravenous injection and 800 to 1,000 mg/kg for oral administration in mice and rats, so that the compound is non-toxic for therapeutic purposes.

The invention therefore provides such compound, a process EXAMPLE Eleven grams (0.035 mol) of 2-methyl-3-(2,3-epoxypropyl)-anilinoquinazolinone-(4) and 4.85 g (0.03 mol) of phenyl-piperazine are dissolved in 30 ml of methanol and boiled for 3% hours. After removal of methanol by distillation, the residue is taken up in methanolic hydrochloric acid, and the dihydrochloride formed is recrystallized twice from ethanol.

The yield of 2-methyl-3-{N-[3-(4-phenyl-piperazinyl( l) '2-hydroxypropyl-( l )]-anilino }-quinazolinone-( 4) dihydrochloride was 9 g. lts melting point is 210 C. For C ,;l-1 N O 2 HC] Calculated: C 60.05%; H 6.07%; N 12.50%; Cl

Found: C 60.26%; H 6.18%; N 12.49%; C1 13.95%.

The free base obtained from the dihydrochloride by dissolving it in dilute sodium hydroxide solution, extracting it with ether, drying the ethereal layer, evaporating off the ether and recrystallizing from ethanol melts at C.

What is claimed is:

1. The compound 2-methyl-3- N-[3-(4-phenylpiperazinyl-( 1))-2-hydroxypropyl-( l )]-anilino -quinazolinone-(4) and its non-toxic acid addition salts.

2. The hydrochloride of the compound specified in claim 1. 

2. The hydrochloride of the compound specified in claim
 1. 